Cu(â…¡)-Mediated Cascade Oxidative C-C Coupling And Aromatization: Synthesis Of3-Hydroxy-Phenanthridinone Derivatives

3-Hydroxy-phenanthridinone derivative is an important class of heterocycles thatcan be found in some biologically active natural products and broadapplication prospects in the field of pharmaceutical and chemical. Therefore, moreand more attention has been paid to the development of novel methods for theassembly of those substituted phenanthridinone derivatives. Based on our previousmethod for the synthesis of carbazolone ring system, we proposed a unique method tosynthesize3-hydroxy-phenanthridinone derivatives via copper acetate-mediatedC(sp~2)-C(sp~3) bond coupling and dehydrogenative aromatization. This methodprovides a method for the preparation of phenanthridinones via the direct C-Hfunctionalization.N-Benzoylated enaminones can be readily prepared through the condensation ofcyclohexane-1,3-dione with substituted amine (such as benzyl amine, ammoniumacetate and substituted aniline) followed by the amide formation from benzoylchloride with the resultant N-aryl enaminone. Various3-hydroxy-phenanthridinonederivatives were furnished via intramolecular C-C bond coupling anddehydrogenative aromatization in the presence of copper acetate inN,N-dimethylacetate. We postulate that the steric hindrance brought by the N-phenylring might benefit the approaching of the N-benzoyl ring to the enone ring, in additionto block the formation of the unexpected carbazolone ring. In order to probe whetheroxidative C-C bond coupling took place prior to the dehydrogenative aromatizationstep, we explored the coupling reaction of the substrate in which two methyl groupswere introduced to the cyclohexenone ring to prevent the occurring of thearomatization step. As expected, the reaction realized the C(sp~2)-C(sp~3) coupling andafforded the desired product.A series of3-hydroxy-phenanthridinone derivatives were synthesized throughthis method. The structures of the compounds were characterized by LRMS,1H&13CNMR spectra and X-ray analysis. Mechanisms were studied for the reaction process,and one possible mechanism was proposed.